The goal of this proposal is to gain a more detailed understanding of the cellular and subcellular processes involved in radiation-induced white matter necrosis through the use of primary cultures of glial cells generated from various portions of the rat CNS. Primary cultures generated from the rat CNS will be manipulated such that they consist of relatively pure populations of a specific type of glial cell (progenitor, oligodendrocyte or astrocyte I) at various stages of differentiation. For the various glial cell phenotypes, the biological consequences of irradiation will be explored in terms of cell death and/or the loss of cell function. In addition, because DNA is considered to be the primary target responsible for radiation-induced cell injury, DNA damage and its repair will be investigated after glial cell irradiation. The goal of these experiments is to elucidate the relationship between DNA damage and repair processes in the various glial cell phenotypes and the biological consequences of radiation. These proposed studies should generate information regarding the response of the various glial cell phenotypes to radiation and thus may provide insights into the pathogenesis of radiation-induced CNS injury.